The acceptance and maintenance of pregnancy is an immunological enigma because the conceptus expresses paternal and embryonic antigens that are foreign to its maternal host yet is not normally rejected. It is increasingly apparent that the fetal-placental allograft is normally afforded protection by immunomodulating factors produced by the reproductive tissues themselves, and by activities of lymphoid and/or myeloid cells associated with or otherwise activated by reproductive tissues. Although the immunologic interactions appear complex and are as yet poorly understood, evidence is accumulating that immunologic recurrent abortion can result from an imbalance or breakdown in these natural immunoprotective mechanisms. Therefore, further knowledge of the relationship between reproductive tissues and the immune system could lead to clinical applications in the treatment of recurrent abortion. The underlying hypothesis of this project is that recurrent spontaneous abortion is mediated by cellular immune mechanisms in a subgroup of women with otherwise unexplained etiology. We propose to apply new immunotechnological reagents to study mechanisms of cell-mediated immunity that may underlie recurrent first trimester spontaneous abortion in women. Immunohistology will be performed with established and new monoclonal antibodies to lymphocyte and monocyte markers to compare immune mediators in the endometrium and decidua of women with recurrent abortion with those in normal controls. Further studies using ELISA and radioimmunoassay techniques will be performed to quantitate lymphokines and monokines present in endometrial/decidual cell extracts and supernatants. Studies will be performed in vitro with activated lymphocytes, macrophages, their supernatants, and purified lymphokines and monokines to determine if cellular and/or soluble immunologic mediators affect the growth nd viability of trophoblast cell lines, mouse embryos and blastocyst outgrowths in vitro. Effective mediators (lymphokines and monokines) will be administered either systemically (tail vein) or locally (uterus) into mice to further study mechanisms of immunologic abortion in vivo. These studies are directed towards a better understanding of cellular and molecular components of immunologic mechanisms underlying human recurrent abortion which should provide insight into its treatment.